Magnetic resonance imaging and spectroscopy are non-invasive techniques that allow probing of soft and hard tissue in humans. In addition to being used as diagnostic tools, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can be utilized in interventional procedures. While proton (1H) MRS and MRI has been employed extensively in brain cancer studies, substantially less research and development has succeeded in extracranial cancer research (particularly breast cancer research) through magnetic resonance spectroscopy, in particular at high magnetic fields (e.g., at or above 3 T), in part because of the relative ease of intracranial MRS as compared with extracranial, even though brain cancer has a relatively low incidence compared to some other types of cancer. For example, breast cancer is the most common malignancy and the number-one leading cause of cancer-related death in women. Each year, nearly 465,000 patients die from breast cancer worldwide, and 1,302,000 more women are newly diagnosed with this disease. Due to its relative good prognosis, nearly 4.4 million breast cancer survivors are living today; however, incidence rates of breast cancer are increasing in most countries. Mortality of breast cancer is mostly associated to metastasis. The current therapeutic interventions typically have limited effect in the treatment of metastatic breast cancer and antiestrogen-chemo- and radiation-resistant tumors. Therefore, early detection is critical in breast cancer management.
A possible reason for having a lesser volume of breast cancer (and other extracranial cancer) research and clinical success through MRS is that several disparate techniques are mature and used customarily at the clinic level, even though such techniques have substantive limitations. For instance, one technique readily employed is mammography, yet mammography screening has a false positive rate about 70%-80%. Ultrasonography is another technique that is often utilized in conjunction with mammography; however, ultrasonography has lower specificity (i.e., more false positives) than mammography. Positron emission tomography/computed tomography (PET/CT) is another technique widely utilized and highly sensitive to detect cancer (e.g., breast cancer) and metastasis for tumors larger than 1 cm; sensitivity decreases significantly for smaller tumors.
Since its first observation about half a century ago, magnetic resonance spectroscopy (MRS) has evolved into a practical technique with a great impact on biology and medicine. It is highly sensitive to the chemical environment of biomolecules and has been used to solve three-dimensional (3D) protein structures and to probe protein dynamics and interactions in aqueous solutions. Magnetic resonance imaging (MRI) detects the tissue water signal for imaging the anatomical organ structures. Because it provides high-resolution anatomical images without the use of ionizing radiation, MRI is powerful in identifying neoplastic changes in soft tissues. The MRI sensitivity for cancer detection can be enhanced by the use of exogenous contrast agents.
Regarding MRS and MRI techniques as applied to breast cancer, proton MRS and MRI techniques can differentiate between benign and malignant breast lesions in vivo. MRI has a high sensitivity (typically greater than 99%) in detecting breast cancer, but low specificity (37%-86%) with a high false-positive rate; MRS can improve breast cancer detection specificity. Currently, choline has been typically the only metabolite that has been observed reliably in human breast cancer by proton MRS, reaching a sensitivity and improved specificity of tumor detection of approximately 78% and 86%, respectively.